Transcranial Pulsed Ultrasound Stimulates Intact Brain Circuits

Tufail, Yusuf; Matyushov, Alexei; Baldwin, N.G.; Tauchmann, Monica L.; Georges, Joseph; Yoshihiro, Anna; Tillery, Stephen I. Helms; Tyler, William J.

doi:10.1016/j.neuron.2010.05.008

Cited by 807 publications

(798 citation statements)

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“…It is possible that the significantly delayed expression of BDNF protein along with induced antiapoptotic Bcl2a1 and Birc3 mRNA would have limited the extent of apoptosis and reactive microglia by 24 h postsonication (65,75). It has been reported that low-intensity pFUS without MB used in neuromodulation studies increased BDNF expression by CA1 and CA3 neurons in the hippocampus within 45 min, stimulating neurogenesis and brain plasticity (76).…”

Section: Discussionmentioning

confidence: 99%

Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Kovács

Kim

Jikaria

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

349

388

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MRI-guided pulsed focused ultrasound (pFUS) combined with systemic infusion of ultrasound contrast agent microbubbles (MB) causes localized blood-brain barrier (BBB) disruption that is currently being advocated for increasing drug or gene delivery in neurological diseases. The mechanical acoustic cavitation effects of opening the BBB by low-intensity pFUS+MB, as evidenced by contrast-enhanced MRI, resulted in an immediate damage-associated molecular pattern (DAMP) response including elevations in heat-shock protein 70, IL-1, IL-18, and TNFα indicative of a sterile inflammatory response (SIR) in the parenchyma. Concurrent with DAMP presentation, significant elevations in proinflammatory, antiinflammatory, and trophic factors along with neurotrophic and neurogenesis factors were detected; these elevations lasted 24 h. Transcriptomic analysis of sonicated brain supported the proteomic findings and indicated that the SIR was facilitated through the induction of the NFκB pathway. Histological evaluation demonstrated increased albumin in the parenchyma that cleared by 24 h along with TUNEL + neurons, activated astrocytes, microglia, and increased cell adhesion molecules in the vasculature. Infusion of fluorescent beads 3 d before pFUS+MB revealed the infiltration of CD68 + macrophages at 6 d postsonication, as is consistent with an innate immune response. pFUS+MB is being considered as part of a noninvasive adjuvant treatment for malignancy or neurodegenerative diseases. These results demonstrate that pFUS+MB induces an SIR compatible with ischemia or mild traumatic brain injury. Further investigation will be required before this approach can be widely implemented in clinical trials.pulsed focused ultrasound | microbubbles | blood-brain barrier | sterile inflammation | magnetic resonance imaging T he temporal proteomic profile in response to blood-brain barrier disruption (BBBD) consists of molecular features that are common across noninfectious insults such as ischemia, trauma, or autoimmune diseases (1-7). The main purpose of the bloodbrain barrier (BBB) is to maintain homeostasis, preventing the passive crossing of cells and molecules that could induce inflammation or damage to cells. The BBB consists of specialized endothelial cells connected through various tight junction proteins (TJP), astrocyte endplates, and a basement membrane. These components form part of the neurovascular unit (NVU) that is comprised of vessels, pericytes, microglia, astrocytes, and neurons along with the extracellular matrix (1,3,4,8). BBBD secondary to ischemia or trauma leads to increases in endothelial caveolae and down-regulation of TJP, transcytosis of plasma proteins (i.e., albumin), and vasogenic edema (1,6,(8)(9)(10)(11). The presence of albumin in the parenchyma following BBBD can activate astrocytes and microglia and induce the production of cytokines, chemokines, and trophic factors (CCTFs) and cell adhesion molecules (CAMs) as observed with a sterile inflammatory response (SIR) to injury (12-15). The release of CCTFs and inte...

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Section: Discussionmentioning

confidence: 99%

Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Kovács

Kim

Jikaria

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

349

388

View full text Add to dashboard Cite

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“…Working with cultured mouse hippocampal slices, the team found that ultrasound triggers nerve impulses by activating voltage-gated sodium and calcium channels 3 . In 2010, the researchers showed that ultrasound could remotely stimulate brain cells in the motor cortices of anaesthetized mice 4 . And a few years later, researchers at INSERM -France's biomedical-research agency based in Paris -replicated the effect in brain areas that control eye movements in conscious monkeys 5 .…”

Section: Early Workmentioning

confidence: 99%

Ultrasound for the brain

Landhuis¹

2017

Nature

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A man comes into the clinic, hands trembling. He can barely write or hold a cup of water. He straps on a specialized head device, lies back and slides into a magnetic resonance imaging (MRI) scanner. Across the room, a physician pushes a button -and the shaking stops. Handed a piece of paper, the man signs his name legibly, hands steady.This kind of transformation is not wishful thinking. Videos documenting such interventions are readily available online. At their heart is a newly approved technology that uses MRI to aim ultrasonic waves -best known for use in prenatal monitoring -at specific areas of the brain. "We can focus the ultrasound through the skull to a part of the thalamus about the size of a grain of rice, " says W. Jamie Tyler, a neuroscientist who studies non-invasive brain stimulation at Arizona State University in Tempe. In that scenario, ultrasound heats and kills neurons in the thalamus, the brain area thought to give rise to a movement disorder called essential tremor, which affects millions of people worldwide. Last year, the US Food and Drug Administration (FDA) approved focused ultrasound thalamotomy as a treatment for people with essential tremor who haven't responded to medication.Today, some scientists are setting their sights on another frontier. By influencing the brain more subtly -zapping small groups of neurons enough to boost or suppress their activity without killing them outright -ultrasound could potentially treat other movement disorders, as well as depression, anxiety and a host of intractable neuropsychiatric disorders, as easily and painlessly as the procedure that calms shaking hands, says Shy Shoham, a biomedical engineer from the Technion-Israel Institute of Technology in Haifa who is starting a lab at New York University Langone Medical Center.The emerging technology, called focusedultrasound neuromodulation, makes use of energies at least an order of magnitude lower than those used for treating tremor. Instead of blasting and killing brain cells, Shoham says, "you basically dial down the system".To some extent, other non-invasive techniques can already do this using magnetic fields or direct electric currents. Transcranial TECHNOLOGY FEATURE © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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“…Tufail et al observed clinical motor contraction following stimulation of the motor cortex of mice, 32 while others have described reversible suppression of visual-evoked potentials using LIFUS. 32 The potential uses of LIFUS not only in neuromodulation but also brain mapping suggest that this is a novel and emerging technology; however, the efficacy and duration of effect of this technique is currently unknown.…”

Section: The Future Of Focused Ultrasound Low-intensity Focused Ultramentioning

confidence: 99%

The Use of Magnetic Resonance Imaging-guided Focused Ultrasound in Movement Disorders—A Review

Talman

Shah

2017

US Endocrinology

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T he use of surgical treatments for movement disorders has been well established for several decades, with a strong focus, in the past, on ablative lesioning procedures and, more recently, deep brain stimulation. Magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) is emerging as a newly recognized surgical technique for the treatment of various movement disorders. The most robust data, demonstrating safety and efficacy of MRgFUS, have been published in trials directed at treatment of essential tremor (ET); however, many trials are underway to define its role in other movement disorders, such as Parkinson's disease with preliminary results echoing those from studies in ET. The full potential for use of MRgFUS, both in the field of movement disorders and beyond, is only beginning to be explored. KeywordsEssential tremor, Parkinson's disease, tremor, thalamotomy, focused ultrasound

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Transcranial Pulsed Ultrasound Stimulates Intact Brain Circuits

Cited by 807 publications

References 64 publications

Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Ultrasound for the brain

The Use of Magnetic Resonance Imaging-guided Focused Ultrasound in Movement Disorders—A Review

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